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Enhanced MHC class II expression in renal proximal tubules precedes loss of renal function in MRL/lpr mice with lupus nephritis

Wuthrich, Rudolf P. and Yui, Mary A. and Mazoujian, Gwen and Nabavi, Nasrin and Glimcher, Laurie H. and Kelley, Vicki E. (1989) Enhanced MHC class II expression in renal proximal tubules precedes loss of renal function in MRL/lpr mice with lupus nephritis. American Journal of Pathology, 134 (1). pp. 45-51. ISSN 0002-9440. PMCID PMC1879559. http://resolver.caltech.edu/CaltechAUTHORS:20170303-154834967

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Abstract

Enhanced MHC class II (Ia) antigen expression is a common feature of autoimmunity. The authors investigated the occurrence of renal Ia expression in MRL/MpJ-lpr/lpr (MRL/lpr) mice with lupus nephritis. By immunoperoxidase staining, normal C3H/FeJ and the congenic strain MRL/MpJ-+/+ express Ia in mononuclear cells in the interstitium only, whereas MRL/lpr with nephritis have abundant Ia expression in proximal tubules (PT), mainly towards the basolateral membrane, and in the characteristic perivascular infiltrates. To a lesser extent, enhanced Ia expression is also observed in the interstitium and in the glomerular mesangium. By Northern blot analysis, the increase in Ia surface determinants correlates with an increased steady-state level of class II mRNA for both I-A and I-E. Ia expression on PT starts focally at around 2-months of age, often in proximity to vascular infiltrates, and precedes overt glomerulo-nephritis and proteinuria. Enhanced class II expression is not restricted to the kidney. MRL/lpr have also increased interstitial class II antigen expression in liver, lung, and spleen compared with normal C3H/FeJ mice. Thus, MRL/lpr mice have enhanced systemic Ia expression, but Ia antigen expression is particularly prominent in PT and may play a key role in the initiation and progression of lupus nephritis.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1879559/PubMed CentralArticle
ORCID:
AuthorORCID
Yui, Mary A.0000-0002-3136-2181
Additional Information:© 1989 American Association of Pathologists. Accepted for publication August 16, 1988. Supported by NIH grants DK-36149 (V.E.K.) and Al-19414 (G.M.), by the Pennsylvania and the Massachusetts Lupus Foundations, and the Jules and Gwen Knapp Charitable Foundation. Rudolf P. Wuthrich is the recipient of a grant from the Swiss National Science Foundation.
Funders:
Funding AgencyGrant Number
NIHDK-36149
NIHAl-19414
Pennsylvania Lupus FoundationUNSPECIFIED
Massachusetts Lupus FoundationUNSPECIFIED
Jules and Gwen Knapp Charitable FoundationUNSPECIFIED
Swiss National Science Foundation (SNSF)UNSPECIFIED
PubMed Central ID:PMC1879559
Record Number:CaltechAUTHORS:20170303-154834967
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20170303-154834967
Official Citation:Wuthrich RP, Yui MA, Mazoujian G, Nabavi N, Glimcher LH, Kelley VE. Enhanced MHC class II expression in renal proximal tubules precedes loss of renal function in MRL/lpr mice with lupus nephritis. The American Journal of Pathology. 1989;134(1):45-51.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74739
Collection:CaltechAUTHORS
Deposited By: Donna Wrublewski
Deposited On:24 Mar 2017 16:31
Last Modified:24 Mar 2017 16:31

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